The present invention relates to a therapeutic agent for primary biliary cirrhosis.
Primary biliary cirrhosis is a liver disease of unknown etiology of middle-aged women, which slowly advances and has, as a background, immunologic abnormality and chief complaints of fatigue, pruritus, jaundice, etc. Primary biliary cirrhosis is an intractable disease different from other diseases in both pathology and method of treatment. Concretely, alcohol-induced liver disease is caused by the intake of alcoholic drinks, and abstinence from alcoholic drinks is the primary selective treatment. The action of alanine contained in xe2x80x9cantagonistic composition alcohol-induced hepatopathyxe2x80x9d which will be described below is to accelerate the alcohol catabolism. Hepatitis, which is not induced by alcoholic drinks, is caused by virus of type A, B or C or by the intake of a large amount of a medicine or the intake of the medicine for a long period of time. For the treatment of hepatitis of such a type, interferon therapy is employed or strong Neo-Minophagen C is used for the treatment. The action of alanine contained in xe2x80x9ctherapeutic agents for hepatitisxe2x80x9d which will be cited below is to inhibit the increase of transaminase by improving the mitochondria function. When these alcohol-induced hepatopathy and hepatitis become chronic, they develop into liver cirrhosis. As for the therapy for liver cirrhosis, only symptomatic therapy for hepatic encephalopathy, hypoalbuminemia and hemorrhage of digestive tracts is possible. However, no therapeutic method for curing liver cirrhosis itself or for inhibiting the advance thereof was developed and, as for alanine, its therapeutic effect on liver cirrhosis is unknown yet.
On the other hand, primary biliary cirrhosis is a liver cirrhosis caused by cholestasis of unknown origin. After the outbreak of the disease, its progress is relatively slow. However, in many of the cases where the symptoms have already been shown, the disease reaches liver cirrhosis in 4 years and the patients die of hepatic insufficiency in about 5 years on average. Patients with primary biliary cirrhosis are thus not convalescing satisfactorily. Although ursodeoxycholic acid is used as the first selective medicine in the treatment of primary biliary cirrhosis, the therapeutic effect thereof is weakened as the conditions of the patients advance. In those advanced stages of diseases, cases in which the symptoms became more serious by the administration of ursodeoxycholic acid were reported. Further, because this disease surely progresses into hepatic insufficiency, patients having the terminal symptoms are obliged to rely on liver transplantation. However, the transplantation has problems such as insufficiency of the organs. Under these circumstances, the development of a medical drug therapy capable of controlling the symptoms and delaying the advance of the disease is demanded. Although it was known to use alanine alone or in combination with other amino acids for preparing a composition for treating patients suffering from alcohol-induced disorders [Japanese Patent Unexamined Published Application (hereinafter referred to as xe2x80x9cJ. P. KOKAIxe2x80x9d No. Sho 63-54320), a composition for treating patients with alcohol-induced liver disorders (J. P.KOKAI No. Hei 5-213746), therapeutic agent for hepatitis (J. P. KOKAI No. Hei 5-221858), liver regeneration accelerator (J. P. KOKAI No. Hei 5-229940), etc., it has never been known that alanine is useful as a therapeutic agent for primary biliary cirrhosis.
The object of the present invention is to provide a therapeutic agent for primary biliary cirrhosis, which can be chronically administrated for a long period of time and exhibits an effect superior to that obtained in ordinary medical therapy.
The present invention was completed on the basis of a finding that when L-alanine was administered to terminal cases (stage IV in Scheuer classification) of primary biliary cirrhosis, the symptoms of which had not been improved by the administration of ursodeoxycholic acid, serum total bilirubin which is one of important indexes as factors which exert influences on the prognosis was improved and excellent therapeutic effects were obtained.
Namely, the present invention provides a therapeutic agent for primary biliary cirrhosis, which contains L-alanine or a pharmaceutically acceptable salt thereof as the active ingredient.